Doravirine Concentrations and Antiviral Activity in Cerebrospinal Fluid in HIV-1 Infected Individuals

HIV-1-infection Clinical Trial

Official title:

Doravirine Concentrations and Antiviral Activity in Cerebrospinal Fluid in HIV-1 Infected Individuals

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04079452
• Other study ID #: DORACeNeS
• Secondary ID: 2018-003915-24
• Status: Completed
• Phase: Phase 3
• Start date: February 18, 2020
• Est. completion date: August 31, 2020

Study information

• Verified date: April 2022
• Source: Fundación FLS de Lucha Contra el Sida, las Enfermedades Infecciosas y la Promoción de la Salud y la Ciencia
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Doravirine is a new HIV-1 non-nucleoside reverse transcriptase inhibitor (NNRTI) that has demonstrated a good efficacy and safety profile in clinical trials. It functions by inhibiting viral replication of both wild-type virus and most common NNRTI variants. It is dosed orally once daily and always given in combination with other HIV-1 active agents as part of highly active antiretroviral therapy. Initial pharmacokinetic studies demonstrated not extensive binding to plasma proteins, which may be crucial determinant for penetration to different reservoirs such as the central nervous system (CNS). This study will address two important issues: The pharmacokinetic profile of Doravirine in cerebrospinal fluid (CSF) as well as the maintenance of HIV suppression in CSF. The assessment of concentrations as well as the antiviral activity of new antiretroviral drugs in compartments such as CNS is relevant to avoid HIV-related neurocognitive disorders as well as for future cure strategies. In addition, the role of unbound ARV drug concentrations has been scarcely evaluated.

Description:

15 asymptomatic, virologically suppressed, HIV infected patients will be offered to switch their antiretroviral treatment to Doravirine+Emtricitabine/TAF. After 4 weeks of treatment all subjects will undergo lumbar puncture and bloods in order to assess CSF and plasma (total and unbound) Doravirine concentrations. HIV RNA also will be assessed. All subjects will complete a follow up visit 4 weeks after

Recruitment information / eligibility

• Status: Completed
• Enrollment: 15
• Est. completion date: August 31, 2020
• Est. primary completion date: August 31, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Asymptomatic, HIV-1 infected individuals = 18 years of age

2. Be on a stable ART continously or =3 consecutive months preceding the screening visit. Patients already receiving TAF/FTC+DoravirineC for at least three consecutive months will be eligible.

3. Plasma HIV-1 RNA at screening <40 copies/mL for at least 3 months at the Screening visit.

4. Signed and dated written informed consent prior to inclusion.

5. Subjects must agree to utilize a highly effective method of contraception during heterosexual intercourse from the screening visit throughout the duration of the study.

Exclusion Criteria:

1. Severe hepatic impairment (Child-Pugh Class C)

2. Ongoing malignancy

3. Active opportunistic infection

4. Primary resistance to any of the ARV included in the study or history of virologic failure with risk of resistance selection to any of the study drugs.

5. Any verified Grade 4 laboratory abnormality

6. ALT or AST = 3xULN and/or bilirubin = 1.5xULN

7. Adequate renal function: Estimated glomerular filtration rate = 50 mL/min

8. Females who are pregnant (as confirmed by positive serum pregnancy test) or breastfeeding.

9. Current treatment with antiaggregant or anticoagulant therapy.

10. History of any neurologic disease/condition/treatment may alter the blood brain barrier permeability.

Related Conditions & MeSH terms

• HIV-1-infection

Intervention

Drug:
• Doravirine
Doravirine 100 mg tablet
• Descovy
Tenofovir alafenamide 25 mg / emtricitabine 200 mg tablet

Locations

Country	Name	City	State
Spain	Hospital Universitari de Bellvitge	L'Hospitalet De Llobregat	Barcelona

Sponsors (3)

Lead Sponsor	Collaborator
Fundación FLS de Lucha Contra el Sida, las Enfermedades Infecciosas y la Promoción de la Salud y la Ciencia	Hospital Universitari de Bellvitge, Institut d'Investigació Biomèdica de Bellvitge

Country where clinical trial is conducted

Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Total Doravirine Concentrations in Cerebrospinal Fluid	Total Doravirine concentrations in cerebrospinal fluid in HIV-1 infected individual receiving ART with Doravirine+FTC/TAF	4 Weeks
Primary	Total Doravirine Concentrations in Blood Plasma	Total Doravirine concentrations in blood plasma	4 Weeks
Primary	Total Doravirine Concentration CSF/Plasma Ratio	total Doravirine CSF/plasma ratio	4 Weeks
Primary	HIV-1 RNA in Cerebrospinal Fluid	Number of patients with HIV-1 RNA cerebrospinal fluid <40 copies/ml	4 Weeks
Primary	HIV-1 RNA in Blood Plasma	Number of patients with HIV-1 RNA in blood plasma <40 copies/ml	4 Weeks
Primary	Unbound Doravirine Concentrations in CSF	Unbound Doravirine concentrations in cerebrospinal fluid in HIV-1 infected individual receiving ART with Doravirine+FTC/TAF	4 Weeks
Primary	Doravirine Concentrations in Blood Plasma	Unbound Doravirine concentrations in blood plasma	4 Weeks
Primary	Unbound Doravirine Concentration CSF/Plasma Ratio	Unbound Doravirine CSF/plasma ratio	4 Weeks